| Atazanavir, sold under the brand name Reyataz among others, is an antiretroviral medication used to treat HIV/AIDS. It is generally recommended for use with other antiretrovirals. It may be used for prevention after a needlestick injury or other potential exposure (postexposure prophylaxis (PEP)). It is taken by mouth.
Common side effects include headache, nausea, yellowish skin, abdominal pain, trouble sleeping, and fever. Severe side effects include rashes such as erythema multiforme and high blood sugar. Atazanavir appears to be safe to use during pregnancy. It is of the protease inhibitor (PI) class and works by blocking HIV protease.
Atazanavir was approved for medical use in the United States in 2003. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication.
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InChI=1S/C38H52N6O7/c1- 37(2,3)31(41-35(48)50-7)33(46)40-29(22-25-14-10-9-11-15-25)30(45)24-44(43-34(47)32(38(4,5)6)42-36(49)51-8)23-26-17-19-27(20-18-26)28-16-12-13-21-39-28/h9-21,29-32,45H,22-24H2,1-8H3,(H,40,46)(H,41,48)(H,42,49)(H,43,47)/t29-,30-,31+,32+/m0/s1 |
| AXRYRYVKAWYZBR-GASGPIRDSA-N |
| COC(=O)N[C@H](C(=O)N[C@@H](Cc1ccccc1)[C@@H](O)CN(Cc1ccc(cc1)-c1ccccn1)NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)C(C)(C)C |
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HIV protease inhibitor
An inhibitor of HIV protease, an enzyme required for production of proteins needed for viral assembly.
antiviral drug
A substance used in the prophylaxis or therapy of virus diseases.
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antiviral drug
A substance used in the prophylaxis or therapy of virus diseases.
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View more via ChEBI Ontology
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dimethyl (3S,8S,9S,12S)-9-benzyl-3,12-di-tert-butyl-8-hydroxy-4,11-dioxo-6-[4-(2-pyridyl)benzyl]-2,5,6,10,13-pentaazatetradecanedioate
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atazanavir
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ChemIDplus
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atazanavirum
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ChEBI
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Latazanavir
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DrugBank
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Zrivada
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DrugBank
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198904-31-3
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CAS Registry Number
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ChemIDplus
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8101951
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Reaxys Registry Number
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Reaxys
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Baril J, Conway B, Giguère P, Ferko N, Hollmann S, Angel JB (2014)
A meta-analysis of the efficacy and safety of unboosted atazanavir compared with ritonavir-boosted protease inhibitor maintenance therapy in HIV-infected adults with established virological suppression after induction.
HIV medicine 15, 301-310 [PubMed:24314017]
[show Abstract]
ObjectivesTreatment simplification involving induction with a ritonavir (RTV)-boosted protease inhibitor (PI) replaced by a nonboosted PI (i.e. atazanavir) has been shown to be a viable option for long-term antiretroviral therapy. To evaluate the clinical evidence for this approach, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating efficacy and safety in patients with established virological suppression.MethodsSeveral databases were searched without limits on time or language. Searches of conferences were also conducted. RCTs were included if they compared a PI/RTV regimen to unboosted atazanavir, after induction with PI/RTV. The meta-analysis was conducted using a random effects model for the proportion achieving virological suppression (i.e. HIV RNA < 50 and <400 HIV-1 RNA copies/mL), CD4 cell counts, lipid levels and liver function tests. Dichotomous outcomes were reported as risk ratios (RRs) and continuous outcomes as mean differences (MDs).ResultsFive studies (n = 1249) met the inclusion criteria. The meta-analysis demonstrated no statistically significant difference in efficacy (i.e. HIV RNA < 50 copies/mL) between PI/RTV and unboosted atazanavir [RR = 1.04; 95% confidence interval (CI) 0.99 to 1.10], with no heterogeneity. Findings were similar in a subanalysis of studies where atazanavir/RTV was the only PI/RTV used during induction. Additional efficacy results support these findings. A significant reduction in total cholesterol (P < 0.00001), triglycerides (P = 0.0002), low-density lipoprotein (LDL) cholesterol (P = 0.009) and hyperbilirubinaemia (P = 0.02) was observed with unboosted atazanavir vs. PI/RTV.ConclusionsThe meta-analysis demonstrated that switching patients with virological suppression from an RTV-boosted PI to unboosted atazanavir leads to improvements in safety (i.e. blood parameter abnormalities) without sacrificing virological efficacy. | Milpied-Homsi B, Moran EM, Phillips EJ (2014)
Antiviral drug allergy.
Immunology and allergy clinics of North America 34, 645-62, ix [PubMed:25017682]
[show Abstract]
Antiviral drugs used to treat HIV and hepatitis C are common causes of delayed drug hypersensitivities for which many of the more severe reactions have been recently shown to be immunogenetically mediated such as abacavir hypersensitivity where HLA-B(∗)57:01 is now used routinely as a screening test to exclude patients carrying this allele from abacavir prescription. Most antiviral drug allergies consist of mild to moderate delayed rash without other serious features (eg, fever, mucosal involvement, blistering rash, organ impairment. In these cases treatment can be continued with careful observation and symptomatic management and the discontinuation rate is low. | Phillips M, Saxon C, Lee V (2014)
Atazanavir and chest pain.
International journal of STD & AIDS 25, 461-464 [PubMed:24108452]
[show Abstract]
We present a case of a 41-year-old man complaining of chest pain, which he directly attributed to his antiretrovirals, specifically atazanavir and ritonavir. The chest pain resolved on stopping the treatment, and recurred when atazanavir was restarted, again resolving on discontinuation. Cardiovascular risk factors are an important consideration with any antiretroviral therapy but particularly with protease inhibitors. The association between atazanavir and cardiac arrhythmias has been reported elsewhere including the British National Formulary, and it may be good practice to perform electrocardiogram assessments in patients commencing and using atazanavir-based regimens. | von Hentig N (2008)
Atazanavir/ritonavir: a review of its use in HIV therapy.
Drugs of today (Barcelona, Spain : 1998) 44, 103-132 [PubMed:18389089]
[show Abstract]
Recommendations for a highly active antiretroviral therapy (HAART) in either pretreated patients or symptomatic patients with an AIDS-defining event are based on a combination of three or more agents from different antiretroviral classes including two nucleoside reverse transcriptase inhibitors with at least one protease inhibitor. The majority of currently available protease inhibitors are coadministered with low-dose ritonavir as a pharmacoenhancer that significantly increases protease inhibitor plasma concentrations. Atazanavir is a highly active azapeptide inhibitor of the HIV protease. It was the first, and to date the only, protease inhibitor designed to be applied once daily (q.d.) and is expected to overcome the problems of earlier agents of this class of drugs, such as unfavorable adverse events like hyperlipidemia, diarrhea and lipodystrophy. Atazanavir, formerly known as BMS-232632, can be dosed either at 400 mg q.d. without a pharmacoenhancer as first-line HIV therapy or combined with ritonavir as atazanavir/ritonavir 300/100 mg q.d. for therapy-experienced patients. The pharmacoenhancing effect of ritonavir on atazanavir resulted in a potent, clinically effective and well-tolerated antiretroviral drug with high plasma concentrations and a sufficient genetic barrier to viral resistance. Nevertheless, noninferiority to lopinavir/ritonavir-containing HAART could not be shown when atazanavir was given unboosted in pretreated patients in the AI424-043 study. When atazanavir was boosted with low-dose ritonavir its efficacy was comparable to that of lopinavir/ritonavir in non-naive patients (AI424-045 study). Additionally, specific side effects were identified during clinical practice, such as an increased rate of patients with jaundice, and, more recently, genetic risk factors causing hyperbilirubinemia. Atazanavir inhibits glucuronyltransferase, an enzyme responsible for the metabolism of bilirubin in liver, thus increasing unconjugated bilirubin levels in blood. However, atazanavir itself also enhances plasma concentrations of other coadministered HIV-1 protease inhibitors, so that its use as a combination partner in boosted double protease inhibitor combinations, with or without the addition of nucleoside reverse transcriptase inhibitors, is being evaluated. Unboosted atazanavir is approved for first-line HIV therapy in adults in the United States, and atazanavir/ritonavir is recommended for the second-line therapy of HIV-1 infection in adult HIV-1-infected patients in the United States and the European Union. More recently, data from the CASTLE study (AI424-138) have been reported at the 15th Conference on Retroviruses and Opportunistic Infections by Molina et al., where boosted atazanavir-containing HAART was compared to a regimen with lopinavir/ritonavir in therapy-naive patients. | Pérez-Elías MJ (2007)
Atazanavir: simplicity and convenience in different scenarios.
Expert opinion on pharmacotherapy 8, 689-700 [PubMed:17376023]
[show Abstract]
HIV protease inhibitors (PI) have undergone the most significant evolution when considering the different families of antiretrovirals. Marketed in 2003, atazanavir (ATV) is the first azapeptide PI, and is considered a member of the second generation of PIs. Important characteristics make ATV different from other drugs in the same family of antiretrovirals. It is administered once daily, either as two capsules (200 mg) or boosted with ritonavir (100 mg) two capsules (150 mg) or one capsule (300 mg). No elevations in serum levels of total cholesterol, low-density lipoprotein cholesterol or triglycerides have been observed with unboosted ATV. Although some increases in these levels are found with boosted ATV, these were lower when compared with other PIs. Elevation in unconjugated bilirubin levels, which is usually not dose limiting, is the most frequent adverse event. Naive patients receiving ATV boosted with ritonavir do not develop PI mutations at failure, whereas unboosted ATV in the same scenario induces the I50L mutation, which does not confer cross-resistance to other PIs. The best scenario for unboosted ATV is simplification. In PI treatment-experienced patients with PI mutations, susceptibility to ATV is usually reduced, so it should be administered with ritonavir. As with other PIs, careful attention must be given to pharmacokinetic drug interactions; the coadministration of certain commonly used drugs among HIV-infected patients, tenofovir and members of the proton pump inhibitor family, leads to significantly lower plasma levels of ATV. | Gianotti N, Soria A, Lazzarin A (2007)
Antiviral activity and clinical efficacy of atazanavir in HIV-1-infected patients: a review.
The new microbiologica 30, 79-88 [PubMed:17619250]
[show Abstract]
Antiretroviral regimens based on human immunodeficiency virus-1 (HIV-1) protease inhibitors (PIs) are hampered by a number of side effects, mainly diarrhea, dyslipidemia, an increased risk of cardiovascular events and diabetes, and lipoaccumulation in the neck and abdomen. Although challenged by these potential untoward effects, PIs are still the cornerstone of highly active antiretroviral therapy (HAART) because of their potency and high genetic barrier. Atazanavir (ATV) is the first once-daily azapeptide HIV-1 PI and can be boosted by ritonavir. The efficacy of ritonavir-boosted ATV (ATV/r)-containing regimens in patients harboring drug-resistant variants is not statistically different from that of the reference PI lopinavir/ritonavir. In Italy, ATV, either boosted or unboosted, is licensed only for drug-experienced patients. However, in clinical trials ATV/r has proved to be effective in treatment-naive HIV-1-infected individuals. There is no evidence that ATV/r-based regimens lead to the selection of mutations conferring cross-resistance to other PIs, and this drug combination has now been included among those recommended by the International AIDS Society-USA Panel and the Department of Health and Human Services (DHHS) Panel as initial treatment when a boosted-PI-based regimen is preferred to a NNRTI-based regimen. | Feldt T, Oette M, Kroidl A, Göbels K, Leidel R, Sagir A, Kuschak D, Häussinger D (2005)
Atazanavir for treatment of HIV infection in clinical routine: efficacy, pharmacokinetics and safety.
European journal of medical research 10, 7-10 [PubMed:15737947]
[show Abstract]
IntroductionAtazanavir (ATV) is a novel protease inhibitor that has been recently introduced into therapy of HIV infection. Currently there is little data on ATV therapy from daily practice.MethodsIn this retrospective study, we report on ATV efficacy and safety in clinical routine. Drug monitoring was performed consisting of unscheduled single measurements and a 4-hour-profile. Trough concentration of >80 ng/ml and peak concentration of 2000-6000 ng/ml were regarded as sufficient.ResultsBetween May 2003 and April 2004, ATV treatment was started in 42 patients, mean observation time was 32 weeks (6-53). Mean age was 45.6 years, 38% had prior AIDS, viral load was undetectable in 73%. Important side effects were minor or moderate diarrhea (27%) and fatigue (15%). ATV was discontinued in 10% due to side effects or malignant diseases. No significant influence on mean values of cholesterol, triglycerides, liver enzymes, CD4-cell-count, and HI-viral load was seen. Virologic failure occurred in 13% of patients, all of them were PI-experienced. Pharmacokinetic data are available for 32 patients, all patients had sufficient trough levels. 30% with unboosted ATV and 21% with boosted ATV had peak plasma concentrations below the level defined as sufficient. Mean trough levels, plasma profile and AUC did not differ significantly between groups with non-boosted versus boosted ATV regimes but showed a wide inter-patient variability.ConclusionsATV treatment of HIV-infected patients with or without a RTV booster was safe and effective in clinical routine. Drug levels were sufficient in the majority of cases. The variability of pharmacokinetic results in our sample supports therapeutic drug monitoring in patients treated with ATV. | Havlir DV, O'Marro SD (2004)
Atazanavir: new option for treatment of HIV infection.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 38, 1599-1604 [PubMed:15156449]
[show Abstract]
Atazanavir is a recently approved human immunodeficiency virus (HIV) protease inhibitor that has an important role in the treatment of both antiretroviral-naive and antiretroviral-experienced individuals. Atazanavir (400 mg) can be administered once per day and requires only 2 capsules. Drug exposure can be safely increased with coadministration of a once-daily regimen of atazanavir (300 mg) and ritonavir (100 mg). Atazanavir is not associated with elevations in serum levels of total cholesterol, low-density lipoprotein cholesterol, or triglycerides, potentially reducing the need for lipid-lowering agents. Atazanavir is associated with elevations in unconjugated bilirubin levels, which are usually not dose limiting. For treatment-naive patients receiving atazanavir who experience virologic rebound, the I50L mutation in HIV protease arises, which does not confer cross-resistance to other protease inhibitors. In treatment-experienced patients with high-level resistance to other protease inhibitors, susceptibility to atazanavir is usually reduced, and optimal effects of atazanavir are seen when it is administered with ritonavir. Similar to other protease inhibitors, careful attention must be paid to drug interactions when administering atazanavir with concomitant medications. | Piliero PJ (2004)
Atazanavir: A novel once-daily protease inhibitor.
Drugs of today (Barcelona, Spain : 1998) 40, 901-912 [PubMed:15645003]
[show Abstract]
Atazanavir (formerly BMS-232632), an azapeptide protease inhibitor (PI), is a new human immunodeficiency virus (HIV) treatment that has recently received marketing approval from the FDA. It has a pharmacokinetic profile that supports once-daily dosing and has demonstrated a unique resistance profile and superior virologic potency compared with other antiretrovirals in vitro. In subjects with HIV, atazanavir (400 mg once daily) produced rapid and sustained improvements in viral load and CD4 counts in both antiretroviral-naive as well as previously treated patients when used in combination with dual nucleoside reverse transcriptase inhibitor (NRTI) treatment. In these studies atazanavir demonstrated comparable anti-HIV efficacy to nelfinavir (twice or three times daily), efavirenz and the combination of ritonavir and saquinavir. However, unlike these comparator agents, atazanavir did not adversely affect the plasma lipid profile, an advantage that sets it apart from other currently available PIs. Atazanavir was inferior to lopinavir/ritonavir in patients who previously failed an initial protease inhibitor containing regimen. Preliminary results in multiple PI-experienced patients indicate comparable efficacy to lopinavir/ritonavir in subjects receiving a boosted regimen of atazanavir plus ritonavir. In summary, atazanavir offers several therapeutic advantages, including a convenient once-daily dosing schedule, neutral lipid effects and a distinct resistance profile. These characteristics may ultimately help improve adherence, reduce the potential risk of long-term cardiovascular events associated with dyslipidemia, and increase the range of therapeutic options available for patients failing other antiretroviral regimens. | Orrick JJ, Steinhart CR (2004)
Atazanavir.
The Annals of pharmacotherapy 38, 1664-1674 [PubMed:15353575]
[show Abstract]
ObjectiveTo review the pharmacology, virology, pharmacokinetics, resistance profile, clinical efficacy, safety, and drug interactions of atazanavir.Data sourcesA PubMed and NLMGateway search (1966-June 2004) utilizing the key words atazanavir and BMS-232632 was performed. Abstracts from scientific meetings, including the Conference on Retroviruses and Opportunistic Infections, International AIDS Society Conference on HIV Pathogenesis and Treatment, Interscience Conference on Antimicrobial Agents and Chemotherapy, and the Infectious Diseases Society of America, were also reviewed.Study selection and data extractionAll publications and meeting abstracts were reviewed, and information relevant to the formulary decision-making process was selected.Data synthesisAtazanavir is a once-daily protease inhibitor (PI) that received approval by the Food and Drug Administration in June 2003. In clinical trials in antiretroviral (ARV)-naïve patients, atazanavir had efficacy similar to that of efavirenz or nelfinavir. In ARV-experienced patients, atazanavir was inferior to lopinavir/ritonavir unless atazanavir was coadministered with low-dose ritonavir. Following failure of an atazanavir-containing regimen in ARV-naïve patients, a unique 150L mutation was seen. Atazanavir resistance is likely when resistance to >/=3 PIs is present. Atazanavir can cause increases in unconjugated bilirubin levels, which rarely leads to jaundice or scleral icterus. In contrast to comparators, atazanavir did not negatively impact the lipid profile. Similar to other PIs, atazanavir is metabolized by and inhibits CYP3A at clinically relevant concentrations; therefore, many potential drug interactions exist.ConclusionsAtazanavir is a once-daily PI that, unlike other PIs, does not negatively impact the lipid profile. Atazanavir may be particularly desirable in patients with hyperlipidemia or other coronary artery disease risk factors. |
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